Project Summary: Dr. Bart Scott is a Research Associate at the Fred Hutchinson Cancer Research Center (FHCRC) and an Acting Clinical Instructor at the University of Washington. His long-term career goal is to be an independent clinical investigator, and his research interests involve improving transplant outcomes in patients with myeloid malignancies. The Career Development Plan is a comprehensive program consisting of institutional meetings, a master's degree in epidemiology, continued training in responsible research, and appropriate evaluation and feedback from an Advisory Committee. Dr. Scott performed a retrospective analysis comparing results with myeloablative and nonmyeloablative regimens in patients with Myelodysplastic Syndrome (MDS) and Acute Myelogenous Leukemia (AML), which serves as the basis for this proposal. The data suggest there are distinct advantages and disadvantages with either approach;only a prospective trial can more definitively address the potential benefits in overall survival. With the mentorship of Drs. Joachim Deeg and Rainer Storb, Dr. Scott has designed and will implement a phase III trial comparing toxicity and efficacy of myeloablative and nonmyeloablative conditioning regimens in patients with MDS and AML. Dr. Scott will be the principal investigator of this trial and will be primarily responsible for all aspects, which include designing consent and assent forms, obtaining IRB approval, collaborating with outside centers, patient accrual, reviewing primary data for eligibility, reporting serious adverse events, and analyzing and publishing data. The specific aims are as follows: 1) determine if there is an overall survival difference in patients with MDS and AML conditioned with myeloablative (cyclophosphamide or fludarabine and busulfan) or nonmyeloablative (fludarabine and low dose total body irradiation) regimens, 2) determine the impact of chemotherapy used for pre-transplant "debulking" on mortality, relapse, and engraftment after myeloablative and nonmyeloablative conditioning, and 3) characterize pharmacokinetics (PK) of intravenous busulfan in the myeloablative regimens, and determine the impact of PK parameters on transplant outcomes. The FHCRC is a leading institution in the treatment of myeloid malignancies and provides an excellent environment to foster the development of Dr. Scott into an independent clinical investigator with expertise in developing and managing clinical trials designed to improve survival and quality of life in patients with myeloid malignancies. Relevance: The goal of this proposal is to improve survival and quality of life in patients with leukemia and related diseases by developing safer and more effective transplant options.